Investigation of Fluoroscopy Time and Radiation Dose by the Number of Cerebral Angiography Operator Experiences.

Objective: We investigated the fluoroscopy time (FT) and radiation dose by the number of cerebral angiography (CA) operator experiences to clarify the learning curve of CA. Methods: The subjects were cases for whom CA was performed at our hospital for 5 years between April 2015 and March 2020. Based on the number of CA operator experiences, they were classified into four groups: 1-50 cases (group A), 51-100 cases (group B), 101-200 cases (group C), and 201 cases and later (group D). The FT and radiation dose were retrospectively investigated. Results: Of the 865 consecutive CA cases, 293 cases for follow-up, i.e. after treatment, 54 for arteriovenous shunt diseases, 21 lacking data, and 1 case requiring intervention for thrombosis during CA were excluded. In total, 496 CA cases were investigated. There were 61 cases in group A, 56 cases in group B, 44 cases in group C, and 335 cases in group D, and there was no significant difference in patient background factors among the groups. The median FT and radiation dose (interquartile range) in each group were 20.2 min (14.6) and 374 mGy (185.3) in group A, 14.8 min (12.1) and 366 mGy (167.9) in group B, 10.8 min (6) and 320 mGy (151.7) in group C, and 9.4 min (6.4) and 336 mGy (171) in group D. The FT was significantly shorter in group C than in group A, and significantly shorter in group D than in groups A, B, and C. The radiation dose was significantly lower in groups C and D than in groups A and B. Conclusion: This study suggested that CA can be performed alone after experiencing approximately 100 cases as an operator.

Induction of large cerebral aneurysms by intraperitoneal administration of ß-aminopropionitrile fumarate in male rats.

BACKGROUND: It is necessary and useful to obtain an experimental model which steadily and rapidly induces aneurysms for investigation of the pathogenesis of cerebral aneurysm. We attempted to examine whether intraperitoneal administration of ß-aminopropionitrile fumarate (BAPN-F) with additional treatments of induced hypertension and hemodynamic stress could steadily and rapidly induce aneurysms in male rats. METHODS: Seven-week-old male Sprague-Dawley rats pretreated with ligation of left common carotid and bilateral posterior renal arteries were administrated BAPN-F intraperitoneally. Induction rate and size of aneurysms was investigated with varying dose and duration of BAPN-F administration (low dose; 400 mg/kg/week for 4 or 8 weeks and high dose; 2800 mg/kg/week for 8 or 12 weeks). RESULTS: Induction rate in the high-dose groups was significantly higher (P<0.01) than that in the low-dose groups. Making comparisons between 8 and 12 weeks of the high-dose groups, while there was no difference in induction rate (8 weeks; 85.2% vs. 12 weeks; 76.9%), aneurysmal size was larger in 12 weeks (8 weeks; 127.5 µm, vs. 12 weeks; 181.7 µm in terms of median) but lethal intrathoracic hemorrhage was increased in 12 weeks (8 weeks; 7.4% vs. 12 weeks; 30.8%). Induction rate of large aneurysm was 22.2% and 30.8% in 8 and 12 weeks of the high-dose groups, respectively. CONCLUSIONS: High-dose BAPN-F administration can cause high-frequency aneurysmal induction. Although there was the difference in size and mortality rate based on administration duration, intraperitoneal administration of 2800 mg/kg/week BAPN-F for 8 weeks would be suitable for aneurysmal induction.

Comparison of Treatment Results by Coil Embolization Procedures for Ruptured Cerebral Aneurysms.

Objective: In coil embolization of ruptured cerebral aneurysms, intraoperative cerebral aneurysm re-rupture and thromboembolism are of concern. A good embolic condition can be expected by adjunctive techniques, but there is an increased risk of complications. We investigated the treatment results by coil embolization procedures for ruptured cerebral aneurysms. Methods: Between January 2016 and December 2019, 75 ruptured saccular cerebral aneurysms were treated by coil embolization at our hospital. The background factors, results of aneurysm embolization, intraoperative re-rupture, symptomatic cerebral embolism, and other factors were investigated retrospectively. We compared and examined these factors based on the procedure. Results: The mean age was 62.8 and there were 57 female patients (76.0%). The single catheter technique (SCT) was used in 44 cases (58.7%) and the adjunctive technique was used in 31 cases (41.3%). Complete obliteration (CO) was achieved in 24 cases (32.0%), there was a neck remnant (NR) in 23 (30.7%), body filling (BF) was observed in 28 (37.3%), intraoperative re-rupture occurred in 7 (9.3%), and symptomatic cerebral embolism developed in 6 (8.0%), but no postoperative re-rupture was observed. Retreatment was required in only three cases of SCT. On comparison by procedure, the incidence of symptomatic cerebral embolism was significantly lower in SCT group than in the adjunctive technique group (2.3% vs 16.1%, p = 0.04). Conclusion: Among the cases of coil embolization for ruptured cerebral aneurysms at our hospital, SCT resulted in a lower incidence of symptomatic cerebral embolism than adjunctive techniques. It is essential to select an appropriate procedure in each case by understanding the characteristics of each procedure.

The Usefulness of Prasugrel as Rescue Medication in Neuroendovascular Therapy.

Objective: In neuroendovascular therapy, clopidogrel resistance and thrombosis are common problems. In such cases, we use prasugrel as rescue medication, and we clarified its usefulness. Methods: We retrospectively investigated 199 consecutive cases of neuroendovascular therapy performed at our hospital from April 2016 to March 2018, and examined the safety and effectiveness of prasugrel. Results: There were 14 cases of prasugrel administration: six cases of coil embolization for cerebral aneurysm, five cases of carotid artery stenting (CAS), and three other cases.The reasons for prasugrel administration were as follows: emergency stent use in four cases, intraoperative thrombosis in three cases, intra-stent thrombosis after CAS in three cases, and others in four cases. In all cases, it was used in combination with aspirin and the median duration of administration was 212 days. Regarding its safety, there was one hemorrhagic complication at the puncture site for which the involvement of prasugrel was unable to be excluded, but it was improved by conservative treatment and there was no major hemorrhage such as intracranial hemorrhage. Regarding its efficacy, in one case, the thrombus during coil embolization did not completely disappear after prasugrel administration and additional mechanical thrombolysis was required. However, no new thrombosis was observed during prasugrel administration in all 14 cases. Conclusion: Prasugrel may be useful as a rescue medication in neuroendovascular therapy.

[Are Localized Lesions in the Common Carotid Artery a Risk Factor for Recurrence of Ischemic Stroke in Patients with Symptomatic Carotid Artery Stenosis?]

BACKGROUND AND PURPOSE: Various studies have addressed risk factors for recurrence of ischemic stroke in patients with symptomatic carotid artery stenosis. However, no investigations have compared common localized carotid artery lesions and internal carotid artery lesions, including carotid bifurcation. This retrospective study investigated risk factors for ischemic stroke recurrence in patients with symptomatic carotid artery stenosis, including a comparison of lesion sites. METHODS: Of 61 consecutive patients admitted to the authors' hospital due to a diagnosis of symptomatic carotid artery stenosis between April 2015 and March 2018, data from 59 were retrospectively reviewed(2 patients diagnosed with arterial dissection were excluded). The primary end point was recurrence of ischemic stroke caused by symptomatic carotid artery stenosis, the cause of the first event. Patients were censored at the time of surgical intervention;events occurring during and after surgical intervention were not included. In the ischemic stroke recurrence and non-recurrence groups, each item was analyzed using the Kaplan-Meier method, and a log-rank test was performed with a significance level set to 5%. RESULTS: Ischemic stroke recurrence before surgical intervention was observed in 5(8.5%)patients. In comparing the recurrence and non-recurrence groups, a significant difference was observed in age(p=0.027)and lesion site(p <0.001). CONCLUSION: A localized lesion in the carotid artery was a risk factor for recurrence of ischemic stroke in patients with symptomatic carotid artery stenosis. For individuals with symptomatic localized lesions in the common carotid artery, surgical intervention should be considered-in addition to medical treatment-regardless of the degree of stenosis.

Characterization of Heparan Sulfate Proteoglycan-positive Recycling Endosomes Isolated from Glioma Cells.

BACKGROUND: Heparan sulfate proteoglycans (HSPGs)-dependent endocytic events have been involved in glioma progression. Thus, comprehensive understanding of the intracellular trafficking complexes formed in presence of HSPGs would be important for development of glioma treatments. MATERIALS AND METHODS: Subcellular fractionation was used to separate vesicles containing HSPGs from the rat C6 glioma cell line. Isolated HSPG-positive vesicles were further characterized with liquid chromatography-mass spectrometry. RESULTS: The HSPG-positive vesicular fractions, distinct from plasma membrane-derived material, were enriched in endocytic marker, Rab11. Proteomic analysis identified more than two hundred proteins to be associated with vesicular membrane, among them, over eighty were related to endosomal uptake, recycling or vesicular transport. CONCLUSION: Part of HSPGs in glioma cells is internalized through clathrin-dependent endocytosis and undergo recycling. The development of compounds regulating HSPG-mediated trafficking will likely enable design of effective glioma treatment.

Efficient Total Synthesis of Bongkrekic Acid and Apoptosis Inhibitory Activity of Its Analogues.

Bongkrekic acid (BKA), isolated from the bacterium Burkholderia cocovenenans, is an inhibitor of adenine nucleotide translocator, which inhibits apoptosis, and is thus an important tool for the mechanistic investigation of apoptosis. An efficient total synthesis of BKA has been achieved by employing a three-component convergent strategy based on Kocienski-Julia olefination and Suzuki-Miyaura coupling. It is noteworthy that segment B has been prepared as a new doubly functionalized coupling partner, which contributes to shortening of the number of steps. Torquoselective olefination with an ynolate has also been applied for the efficient construction of an unsaturated ester. Furthermore, it is revealed that 1-methyl-2-azaadamantane N-oxyl is an excellent reagent for final oxidation to afford BKA in high yield. Based on the total synthesis, several BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the apoptosis inhibitory activity of BKA. More easily available BKA analogues with potent apoptosis inhibitory activity were also developed.

Utility of early post-treatment single-photon emission computed tomography imaging to predict outcome in stroke patients treated with intravenous tissue plasminogen activator.

It is important to predict the outcome of tissue plasminogen activator (tPA)-treated patients early after the treatment for considering the post-tPA treatment option. We assessed cerebral blood flow (CBF) of tPA-treated patients with single-photon emission computed tomography (SPECT) 1 hour after tPA infusion to predict the patient outcome. Technetium-99m-hexamethylpropyleneamine oxime SPECT was performed in 35 consecutive tPA-treated patients. Asymmetry index, a contralateral-to-ipsilateral ratio of CBF, was calculated to analyze CBF quantitatively. Hypoperfusion or hyperperfusion was defined as a decrease of 25% or more or a increase of 25% or more in asymmetry index, respectively. Of all 35 patients, 23 had only hypoperfusion, 8 had both hypoperfusion and hyperperfusion, 2 had only hyperperfusion, and 2 had no perfusion abnormality. When evaluating the association between hypoperfusion and outcome, hypoperfusion volumes were significantly correlated with the modified Rankin Scale at 3 months (r = .634, P < .001). Hyperperfusion was observed in 10 patients (28.6%) and they showed a marked National Institutes of Health Stroke Scale score improvement in the first 24-hour period, which were significantly greater than those of 25 patients without hyperperfusion (P = .033). Eight patients (22.9%) with intracerebral hemorrhage (ICH) were all asymptomatic. Most ICHs were located in hypoperfusion areas, and no ICH was related to hyperperfusion. The results of the present study demonstrated that hypoperfusion volume was associated with poor outcome, whereas the presence of hyperperfusion seemed to be predictive of symptom improvement but not of development of ICH. Taken together, early post-treatment SPECT imaging seems to be a useful biomarker of outcome in tPA-treated patients.

Mitochondrial delivery of bongkrekic acid using a MITO-Porter prevents the induction of apoptosis in human HeLa cells.

The fact that mitochondrial dysfunction has been implicated in a variety of human diseases suggests that they would be expected as a target organelle for these diseases. Bongkrekic acid (BKA) is a chemical that functions as a ligand of the adenine nucleotide translocator and is known to potently inhibit the mitochondrial permeability transition that is associated with apoptosis. Thus, delivering it to mitochondria would be an innovative therapy for the treatment of mitochondrial diseases that are largely associated with apoptosis. Here, we report on the use of a MITO-Porter, an innovative nanocarrier for mitochondrial delivery via mitochondrial membrane fusion, for delivering BKA to mitochondria. We first constructed a BKA-MITO-Porter, in which BKA is contained in lipid envelopes of a MITO-Porter. We then confirmed that the BKA-MITO-Porter was efficiently internalized into cells and is delivered to mitochondria, similar to a conventional MITO-Porter. Moreover, we evaluated the antiapoptosis effect of the BKA-MITO-Porter in HeLa cells by measuring caspase 3/7 activity. The findings confirmed that the BKA-MITO-Porter showed a strong antiapoptosis effect compared with naked BKA. The results reported here demonstrate its potential for the use in therapies aimed at mitochondrial diseases, as a mitochondrial medicine candidate.

[A case of combined glossopharyngeal and trigeminal neuralgia].

It is well-known that idiopathic neuralgias of the trigeminal and glossopharyngeal nerves are caused by vascular compression at the root entry zone of the cranial nerves. Because they are functional diseases, initial treatment is medical, especially with carbamazepine. However, if medical therapy fails to adequately manage the pain, microvascular decompression (MVD) is prescribed. Glossopharyngeal neuralgia is rare, and combined trigeminal and glossopharyngeal neuralgia is an extremely rare disorder. A 70-year-old woman presented herself to Hokkaido Neurosurgical Memorial Hospital because of paroxysms of lancinating pain in her left pharynx and another lancinating pain in her left cheek. Carbamazepine, which was prescribed at another hospital, favorably relieved the pain; however, drug eruption compelled her to discontinue the medication. The multi-volume method revealed that a root entry zone of the left glossopharyngeal nerve was compressed by the left posterior inferior cerebellar artery, and the left trigeminal artery was compressed by the left superior cerebellar artery. MVD for both nerves was performed employing a left lateral suboccipital craniotomy. She experienced complete relief of pain immediately after MVD. Combined trigeminal and glossopharyngeal neuralgia is extremely rare, but some groups noted a relatively high incidence of concurrent trigeminal neuralgia in patients with glossopharyngeal neuralgia up until the 1970's. Glossopharyngeal neuralgia includes pain near the gonion; therefore, there is an overlap of symptoms between glossopharyngeal and trigeminal neuralgias. By virtue of recent progress in imaging technology, minute preoperative evaluations of microvascular compression are possible. Until the 1970's, there might have been some misunderstanding regarding the overlap of symptoms because of lack of the concept of microvascular compression as a cause of neuralgia and rudimentary imaging technology. Minute evaluations of both symptoms and imaging are very important.

[Case of direct carotid-cavernous fistula presenting with subarachnoid hemorrhage].

We report a case of longstanding asymptomatic direct carotid-cavernous fistula (CCF) which caused fatal subarachnoid hemorrhage (SAH). A 91-year-old female with no history of previous head trauma and optic symptoms presented acute subarachnoid hemorrhage. Angiography revealed a left direct carotid-cavernous fistula draining only into the contralateral cavernous sinus with leptomeningeal venous reflux and small varix on the pontine bridging vein. The affected cavernous sinus was markedly dilated and there was no septum between the left cavernous sinus and the internal carotid artery. The patient underwent transvenous coil embolization for intercavernous sinus and leptomeningeal venous reflux was successfully obliterated and opacification of the varix was diminished. The past history of this patient and angiographical findings strongly suggest long standing asymptomatic CCF caused SAH.

Expression of thioredoxin-1 and hypoxia inducible factor-1α in cerebral arteriovenous malformations: Possible role of redox regulatory factor in neoangiogenic property.

BACKGROUND: Recently it is reported that proliferative activity remains in vascular walls of cerebral arteriovenous malformations (AVMs). These reports indicate that endothelial cells in AVMs have the neoangiogenic property. In this study, we assess the role of thioredoxin-1 (Trx-1) and hypoxia-inducible factor 1a (HIF-1α) in AVMs. These factors are reported to play a role in neoangiogenesis. METHODS: We analyzed the expressions of Trx1 in the specimens of human cerebral AVMs. In addition, we also analyzed the expression of HIF-1α in these specimens by immunohistochemical method and RT-PCR. Furthermore, we assessed the effect of redox state and expression of Trx-1 during neoangiogenesis using in vitro angiogenesis assay. FINDINGS: Trx-1 and HIF-1α immunoreactivity was detected in almost all 17 specimens of AVMs. Trx-1 and HIF-1α immunoreactive cells were distributed mainly endothelium of intranidal arteries and enlarged veins with thickened vascular walls. Double staining shows that Trx-1 and VEGF (vascular endothelial growth factor) immunoreactivity were colocalized in the same cells. These cells were considered to be endothelial cells. HIF-1α immunoreactivity was also colocalized with VEGF immunoreactivity in endothelium. As for influencing factors, the presence of deep drainers and convulsion significantly associated with HIF-1α expression. Trx-1 assessed by western blotting decreased at 6 hours and 12 hours after plating on Matrigel, which is a model of angiogenesis. CONCLUSIONS: We have shown that the endothelial induction of Trx-1 and HIF-1α in cerebral AVMs. Based on all findings obtained in this study, Trx-1 may affect the neoangiogenic property of cerebral AVMs.

The efficacy of apolipoprotein E deficiency in cerebral aneurysm formation.

Subarachnoid hemorrhage due to the rupture of a cerebral aneurysm is a life-threatening disease. Despite this, the detailed mechanisms underlying the initiation and progression of cerebral aneurysm are unclear. The relation of hypercholesterolemia and apolipoprotein E (ApoE) to cerebral aneurysm formation, has been unclear until now. We used, in the present study, a previously established cerebral aneurysm model of rats and mice whose histological features were closely similar to human cerebral aneurysms. ApoE protein was expressed mainly in the endothelial cells of arterial walls both in control arteries and cerebral aneurysms. The expression of ApoE was reduced during aneurysm formation in the immunohistochemistry. The mRNA expression of ApoE in arterial walls was not different between the controls and cerebral aneurysms. Owing to the deficiency of ApoE, mice presented marked hypercholesterolemia, but there was no difference in cerebral aneurysm formation. In the present study, we clarified that ApoE was not responsible for cerebral aneurysm formation.

Gene expression during the development of experimentally induced cerebral aneurysms.

Cerebral aneurysms are a major cause of subarachnoid hemorrhage, but the mechanism of their development remains unclear. In this study, we investigated candidate genes whose expression is significantly changed during the development of experimentally induced cerebral aneurysms using adaptor-tagged competitive polymerase chain reaction (ATAC-PCR). Twenty-four rats received sham operation (control) or the operation for the induction of experimental cerebral aneurysms. Rats were sacrificed at time 0, 2 weeks, 1 month and 3 months after the operation (n = 6 for each group). RNAs from right anterior cerebral artery/olfactory artery (ACA/OA) bifurcations were assessed via a 191-gene data matrix expression profile by ATAC-PCR. We identified 15 genes whose expression is significantly altered during cerebral aneurysm formation, including major heparan sulfate proteoglycan, cathepsin B, hevin and beta(4)-integrin. We also confirmed protein expression of beta(4)-integrin in rat cerebral aneurysms by quantitative real-time PCR and immunohistochemistry. The ATAC-PCR revealed temporal changes in gene expression during the development of experimental cerebral aneurysms. The genes that were significantly changed in this study would be the candidates for future studies concerning the development of cerebral aneurysms.

NF-kappaB is a key mediator of cerebral aneurysm formation.

BACKGROUND: Subarachnoid hemorrhage caused by the rupture of cerebral aneurysm (CA) remains a life-threatening disease despite recent diagnostic and therapeutic advancements. Recent studies strongly suggest the active participation of macrophage-mediated chronic inflammatory response in the pathogenesis of CA. We examined the role of nuclear factor-kappaB (NF-kappaB) in the pathogenesis of CA formation in this study. METHODS AND RESULTS: In experimentally induced CAs in rats, NF-kappaB was activated in cerebral arterial walls in the early stage of aneurysm formation with upregulated expression of downstream genes. NF-kappaB p50 subunit-deficient mice showed a decreased incidence of CA formation with less macrophage infiltration into the arterial wall. NF-kappaB decoy oligodeoxynucleotide also prevented CA formation when it was administered at the early stage of aneurysm formation in rats. Macrophage infiltration and expression of downstream genes were dramatically inhibited by NF-kappaB decoy oligodeoxynucleotide. In human CA walls, NF-kappaB also was activated, especially in the intima. CONCLUSIONS: Our data indicate that NF-kappaB plays a crucial role as a key regulator in the initiation of CA development by inducing some inflammatory genes related to macrophage recruitment and activation. NF-kappaB may represent a therapeutic target of a novel medical treatment for CA.

Role of TIMP-1 and TIMP-2 in the progression of cerebral aneurysms.

BACKGROUND AND PURPOSE: The degradation of extracellular matrix (ECM) is a hallmark of a cerebral aneurysm; however, little is known regarding the molecular mechanism leading to this change. Tissue inhibitor of matrix metalloproteinase (TIMP) regulates the ECM degradation in vascular walls by inhibiting the activity of matrix metalloproteinases (MMPs). We investigated the role of TIMPs in the progression of cerebral aneurysms in the present study. METHODS: TIMP-1 and TIMP-2 expression was examined by immunohistochemistry and quantitative RT-PCR in experimentally-induced cerebral aneurysms in rats. The incidence of aneurysmal changes in TIMP-1(-/-) and TIMP-2(-/-) mice was compared with that in the wild-type mice. RESULTS: TIMP-1 and TIMP-2 were expressed mainly by smooth muscle cells in aneurysmal walls. Quantitative PCR showed an increase of TIMP-1 and TIMP-2 mRNA in the early stage of aneurysm progression (form 0 to 1 month) but not in the late stage (form 1 to 3 months), whereas mRNA expression of MMP-2 and MMP-9 dramatically increased in the late stage. In both TIMP-1(-/-) mice and TIMP-2(-/-) mice, aneurysm progression was promoted with the increased enzyme activity of MMPs. CONCLUSIONS: Our findings suggest that TIMP-1 and TIMP-2 have a protective role for the progression of cerebral aneurysms. There is an imbalance between MMPs and TIMPs in the late stage of cerebral aneurysm formation, which may be responsible for ECM degradation leading to the progression and rupture of cerebral aneurysms.

Cerebral aneurysm progression suppressed by blockage of endothelin B receptor.

OBJECT: Cerebral aneurysm is a major cause of subarachnoid hemorrhage, but the mechanisms of its development remain unclear. Mechanical stretch has been reported to induce vascular smooth-muscle cell apoptosis via endothelin B receptors (ETBRs). The objectives of this study were to clarify the expression and localization of ETBR in cerebral aneurysms and to examine the effect of ETBR blockage on the development of experimental cerebral aneurysms. METHODS: Seventy-two rats underwent a cerebral aneurysm induction procedure and were divided into four groups according to the duration of postoperative study periods. Expression of ETBR was confirmed by reverse transcription-polymerase chain reaction and immunohistochemical analysis. The authors also studied the effect of K-8794, an oral selective antagonist of ETBR, to see whether it would influence the formation of cerebral aneurysms. Two weeks after the aneurysm induction procedure, ETBR was rarely detected in anterior cerebral artery-olfactory artery bifurcations, but it was weakly expressed in experimental cerebral aneurysms at 1 month after the procedure, and markedly expressed at 3 months. The administration of K-8794 for 1 month after the procedure significantly reduced the number of advanced aneurysms and the number of apoptotic smooth-muscle cells. CONCLUSIONS: These results suggest that ETBR might play a significant role in the progression of cerebral aneurysms and have the potential to improve prevention and treatment of cerebral aneurysms.

Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage caused by cerebral aneurysm rupture remains a life-threatening emergency despite advances in treatment. However, the mechanisms underlying aneurysm initiation, progression, and rupture remain unclear. We developed a method to induce experimental cerebral aneurysms in rats, monkeys, and mice. Interleukin-1beta (IL-1beta) is a key inflammatory mediator, and it is thought to be a promising target for the treatment of inflammatory diseases. In the present study, we examined the role of IL-1beta in cerebral aneurysm development. METHODS: Cerebral aneurysms were experimentally induced in 5-week-old male C57BL/6 mice, IL-1beta gene-deficient (IL-1beta-/-) mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were dissected and examined histologically and immunohistochemically. RESULTS: IL-1beta was expressed in vascular media in mice at an early stage of aneurysmal models' cerebral arteries. No differences were seen in the rate of aneurysm development between IL-1beta-/- and wild-type mice, but the percentage of advanced aneurysm change was significantly larger in wild-type animals. Furthermore, in IL-1beta-/- mice, increased caspase-1 expression was seen compared with wild-type animals. Additionally, the number of apoptotic cells assessed by single-stranded DNA immunoreactivity and TUNEL was significantly reduced in IL-1beta-/- mice compared with wild-type animals. CONCLUSIONS: IL-1beta is important for the progression of cerebral aneurysms in a mouse model. Disruption of the IL-1beta gene results in the reduced incidence of mature experimental cerebral aneurysms.